Method and apparatus for EPROI using T1e spin-lattice relaxation response

Abstract

An apparatus and method for improved S/N measurements useful for electron paramagnetic resonance imaging in situ and in vivo, using high-isolation transmit/receive surface coils and temporally spaced pulses of RF energy (e.g., in some embodiments, a RF pi pulse) having an amplitude sufficient to rotate the magnetization by 180 degrees followed after varied delays, by a second RF pulse having an amplitude half that of the initial pulse to rotate the magnetization by, e.g., 90 degrees (a pi/2 pulse), to the plane orthogonal to the static field where it evolves for a short time. Then a third RF pi pulse sufficient to rotate the magnetization by, e.g., 180 degrees, forms an echo (in some embodiments, the second and third pulses are from the same signal as the first pulse but are phase shifted by 0, 90, 180, or 270 degrees to reduce signal artifact), to image human body.

What is claimed is: 
     
       1. A method for electron paramagnetic resonance oxygen imaging (EPROI) of a volume of animal tissue in vivo in an animal, the method comprising:
 placing a reporter molecule in the animal; 
 establishing a static (DC) magnetic field on the volume of animal tissue, wherein the establishing of the static (DC) magnetic field includes generating electron-spin-aligning constant and gradient magnetic fields with a set of static magnetic-field coils; 
 generating a plurality of pulse sets that elicit a T 1e  spin-lattice relaxation response from the volume of tissue, wherein the generating of each one of the plurality of pulse sets includes:
 generating a first RF excitation magnetic field pulse having a plurality of RF cycles in a first direction orthogonal to the static (DC) magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue, 
 delaying for a first delay time, 
 generating a second RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, 
 delaying for a second delay time, 
 generating a third RF excitation magnetic field pulse having a plurality of RF cycles in the first direction generally orthogonal to the static (DC) magnetic field, and 
 delaying for a third delay time; and 
 
 sensing an RF spin-relaxation signal, and 
 generating a received electrical signal based on the sensed RF signal, 
 generating an EPROI image of oxygen in the animal using the T 1e  response, wherein the first, second and third RF excitation magnetic field pulses are of magnitudes and durations configured to measure T 1e  spin-lattice relaxation in the volume of tissue, and wherein for each of the plurality of pulse sets:
 the first RF excitation magnetic field pulse is a pi pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin by pi radians; 
 the second RF excitation magnetic field pulse is a pi/2 pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin ½ pi radians; and 
 the third RF excitation magnetic field pulse is a pi pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin pi radians. 
 
 
     
     
       2. The method of  claim 1 , wherein for each of the plurality of pulse sets, the first, second and third RF excitation magnetic field pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence. 
     
     
       3. The method of  claim 1 , further comprising:
 digitally signal processing the received electrical signal to generate image data; 
 storing the image data; and 
 displaying the image data. 
 
     
     
       4. The method of  claim 1 , wherein the animal tissue is human tissue in a living human. 
     
     
       5. A method for electron paramagnetic resonance oxygen imaging (EPROI) of a volume of animal tissue in vivo in an animal, the method comprising:
 placing a reporter molecule in the animal; 
 establishing a static (DC) magnetic field on the volume of animal tissue; 
 applying an RF three-pulse sequence that elicits an inversion-recovery T 1e  spin-lattice relaxation response from the volume of tissue; 
 generating an EPROI image of oxygen in the animal based on the inversion-recovery T 1e  spin-lattice relaxation response, wherein the establishing of the static (DC) magnetic field includes generating electron-spin-aligning constant and gradient magnetic fields with a set of static magnetic-field coils, and wherein the applying of the RF three-pulse sequence further includes:
 generating a plurality of pulse sets, wherein the generating of each one of the plurality of pulse sets includes:
 generating a first RF excitation magnetic field pulse having a plurality of RF cycles in a first direction orthogonal to the static (DC) magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue, 
 delaying for a first delay time, 
 generating a second RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, 
 delaying for a second delay time, 
 generating a third RF excitation magnetic field pulse having a plurality of RF cycles in the first direction generally orthogonal to the static (DC) magnetic field, and 
 delaying for a third delay time; 
 
 
 sensing an RF spin-relaxation signal; and 
 generating a received electrical signal based on the sensed RF signal, wherein the first, second and third RF excitation magnetic field pulses are of magnitudes and durations configured to measure T 1e  spin-lattice relaxation in the volume of tissue, 
 
       wherein for each of the plurality of pulse sets,
 the first, second and third RF excitation magnetic field pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence having a π-pulse as the first pulse, a T delay as the first delay, a π/2-pulse as the second pulse, a τ delay as the second delay, a π-pulse as the third pulse, a τ delay as the third delay, wherein the first, second and third pulses are each about 35 ns in duration, 
 wherein the π/2 pulse rotates a magnetization π/2 radians and the π-pulses rotate a magnetization π radians, 
 wherein τ=630 ns, 
 wherein T has a value in a range of about 500 ns to about 16,000 ns, and 
 wherein the cycles of RF have a frequency of about 250 MHz. 
 
     
     
       6. The method of  claim 5 , further comprising:
 digitally signal processing the received electrical signal to generate image data; 
 storing the image data; and 
 displaying the image data. 
 
     
     
       7. A method for electron paramagnetic resonance oxygen imaging (EPROI) of a volume of animal tissue in vivo in an animal, the method comprising:
 placing a reporter molecule in the animal; 
 establishing a static (DC) magnetic field on the volume of animal tissue; 
 applying an RF three-pulse sequence that elicits an inversion-recovery T 1e  spin-lattice relaxation response from the volume of tissue; 
 generating an EPROI image of oxygen in the animal based on the inversion-recovery T 1e  spin-lattice relaxation response, wherein the establishing of the static (DC) magnetic field includes generating electron-spin-aligning constant and gradient magnetic fields with a set of static magnetic-field coils, and wherein the applying of the RF three-pulse sequence further includes:
 generating a plurality of pulse sets, wherein the generating of each one of the plurality of pulse sets includes:
 generating a first RF excitation magnetic field pulse having a plurality of RF cycles in a first direction orthogonal to the static (DC) magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue, 
 delaying for a first delay time, 
 generating a second RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, 
 delaying for a second delay time, 
 generating a third RF excitation magnetic field pulse having a plurality of RF cycles in the first direction generally orthogonal to the static (DC) magnetic field, and 
 delaying for a third delay time; 
 
 
 sensing an RF spin-relaxation signal; and 
 generating a received electrical signal based on the sensed RF signal, wherein the first, second and third RF excitation magnetic field pulses are of magnitudes and durations configured to measure T 1e  spin-lattice relaxation in the volume of tissue, 
 
       wherein for each of the plurality of pulse sets,
 the first, second and third RF excitation magnetic field pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence having a π-pulse as the first pulse, a T delay as the first delay, a π/2-pulse as the second pulse, a τ delay as the second delay, a π-pulse as the third pulse, a τ delay as the third delay, wherein the first, second and third pulses are each about 35 ns in duration, 
 wherein the π/2 pulse rotates a magnetization π/2 radians and the π-pulses rotate a magnetization π radians, 
 wherein τ=630 ns, 
 wherein T has a value in a range of about 500 ns to about 16,000 ns, 
 wherein the cycles of RF have a frequency of about 250 MHz, 
 wherein the plurality of pulse sets apply a sixteen-step phase cycling, 
 wherein about 7520 acquisitions are acquired per value of T and include phase cycling, 
 wherein eight T values that are approximately logarithmically spaced between one-half microseconds (0.5 μs) and sixteen microseconds (16 μs) are used, 
 wherein T LF   R =25 μs, and 
 wherein the phase cycling uses values selected according to the following table: 
 
       
         
           
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                     
                 
                     
                     
                     
                     
                     
                     
                     
                   Detection 
                   Detection 
                 
                     
                   First 
                   First 
                   Second 
                   Second 
                     
                   Third 
                   channel 
                   channel Im 
                 
                   N 
                   pulse 
                   delay 
                   pulse 
                   delay 
                   Third pulse 
                   delay 
                   Re (real) 
                   (imaginary) 
                 
                     
                 
                     
                 
                 
                 
                 
                 
                 
                 
                 
                 
                 
               
                   1 
                   X 
                   T 
                   0.5X 
                   630 ns 
                   X 
                   630 ns 
                   A 
                   B 
                 
                   2 
                   X 
                   T 
                   0.5X 
                   630 ns 
                   −X 
                   630 ns 
                   A 
                   B 
                 
                   3 
                   X 
                   T 
                   0.5X 
                   630 ns 
                   Y 
                   630 ns 
                   −A 
                   −B 
                 
                   4 
                   X 
                   T 
                   0.5X 
                   630 ns 
                   −Y 
                   630 ns 
                   −A 
                   −B 
                 
                   5 
                   X 
                   T 
                   −0.5X 
                   630 ns 
                   X 
                   630 ns 
                   −A 
                   −B 
                 
                   6 
                   X 
                   T 
                   −0.5X 
                   630 ns 
                   −X 
                   630 ns 
                   −A 
                   −B 
                 
                   7 
                   X 
                   T 
                   −0.5X 
                   630 ns 
                   Y 
                   630 ns 
                   A 
                   B 
                 
                   8 
                   X 
                   T 
                   −0.5X 
                   630 ns 
                   −Y 
                   630 ns 
                   A 
                   B 
                 
                   9 
                   X 
                   T 
                   0.5Y 
                   630 ns 
                   X 
                   630 ns 
                   B 
                   −A 
                 
                   10 
                   X 
                   T 
                   0.5Y 
                   630 ns 
                   −X 
                   630 ns 
                   B 
                   −A 
                 
                   11 
                   X 
                   T 
                   0.5Y 
                   630 ns 
                   Y 
                   630 ns 
                   −B 
                   A 
                 
                   12 
                   X 
                   T 
                   0.5Y 
                   630 ns 
                   −Y 
                   630 ns 
                   −B 
                   A 
                 
                   13 
                   X 
                   T 
                   −0.5Y 
                   630 ns 
                   X 
                   630 ns 
                   −B 
                   A 
                 
                   14 
                   X 
                   T 
                   −0.5Y 
                   630 ns 
                   −X 
                   630 ns 
                   −B 
                   A 
                 
                   15 
                   X 
                   T 
                   −0.5Y 
                   630 ns 
                   Y 
                   630 ns 
                   B 
                   −A 
                 
                   16 
                   X 
                   T 
                   −0.5Y 
                   630 ns 
                   −Y 
                   630 ns 
                   B 
                   −A 
                 
                     
                 
             
                
                
                
                
                
               
               
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
       8. The method of  claim 7 , further comprising:
 digitally signal processing the received electrical signal to generate image data; 
 storing the image data; and 
 displaying the image data. 
 
     
     
       9. A method for electron paramagnetic resonance oxygen imaging (EPROI) of a volume of animal tissue in vivo in an animal, the method comprising:
 placing a reporter molecule in the animal; 
 establishing a static (DC) magnetic field on the volume of animal tissue; 
 applying an RF three-pulse sequence that elicits a T 1e  spin-lattice relaxation response from the volume of tissue; and 
 generating an EPROI image of oxygen in the animal based on the T 1e  spin-lattice relaxation response, wherein the establishing of the static (DC) magnetic field includes generating electron-spin-aligning constant and gradient magnetic fields with a set of static magnetic-field coils, and wherein the applying of the RF three-pulse sequence further includes: 
 generating a plurality of pulse sets, wherein the generating of each one of the plurality of pulse sets includes:
 generating a first RF excitation magnetic field pulse having a plurality of RF cycles in a first direction orthogonal to the static (DC) magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue, 
 delaying for a first delay time, 
 generating a second RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, 
 delaying for a second delay time, 
 generating a third RF excitation magnetic field pulse having a plurality of RF cycles in the first direction generally orthogonal to the static (DC) magnetic field, and 
 delaying for a third delay time; and 
 
 
       wherein the method further includes:
 sensing an RF spin-relaxation signal, and 
 generating a received electrical signal based on the sensed RF signal, 
 wherein the first, second and third RF excitation magnetic field pulses are of magnitudes and durations configured to measure the T 1e  spin-lattice relaxation response in the volume of tissue, and wherein for different ones of the plurality of pulse sets, the second RF excitation magnetic field pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees for different ones of the plurality of pulse sets) relative to the first pulse, and the third pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees) relative to the first pulse. 
 
     
     
       10. The method of  claim 9 , further comprising:
 digitally signal processing the received electrical signal to generate image data; 
 storing the image data; and 
 displaying the image data. 
 
     
     
       11. A method for electron paramagnetic resonance oxygen imaging (EPROI) of a volume of animal tissue in vivo in an animal, the method comprising:
 placing a reporter molecule in the animal; 
 establishing a static (DC) magnetic field on the volume of animal tissue; 
 transmitting an RF three-pulse sequence from a set of surface transmit coils, wherein the transmitted RF three-pulse sequence generates an excitation magnetic field in the volume of animal tissue and elicits a T 1e  spin-lattice relaxation response from the volume of tissue; 
 receiving a set of RF signals from a set of surface receive coils, wherein the set of surface receive coils generates a sensed electrical signal in response to a sensed magnetic field in the volume of animal tissue, and wherein the set of transmit coils and the set of receive coils are oriented relative to one another such that the sensed electrical signal has little or no component directly due to the excitation magnetic field, and wherein the set of surface receive coils is configured to detect electron paramagnetic resonance signals in the volume of animal tissue; and 
 generating an EPROI image of oxygen in the animal from the electron paramagnetic resonance signals using the T 1e  response, 
 wherein the establishing of the static (DC) magnetic field includes generating electron-spin-aligning constant and gradient magnetic fields with a set of static magnetic-field coils; and 
 wherein the transmitting of the RF three-pulse sequence further includes: 
 generating a plurality of pulse sets, wherein the generating of each one of the plurality of pulse sets includes:
 generating a first RF excitation magnetic field pulse having a plurality of RF cycles in a first direction orthogonal to the static (DC) magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue, and having a magnitude and duration selected to rotate an electron paramagnetic resonance spin by pi radians, 
 delaying for a first delay time, 
 generating a second RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, and having a magnitude and duration selected to rotate an electron paramagnetic resonance spin ½ pi radians, 
 delaying for a second delay time, 
 generating a third RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, and having a magnitude and duration selected to rotate an electron paramagnetic resonance spin pi radians; and 
 delaying for a third delay time. 
 
 
     
     
       12. The method of  claim 11 , wherein the transmitted RF three-pulse sequence forms an inversion recovery with electron-spin echo detection (IRESE) sequence. 
     
     
       13. The method of  claim 11 , wherein the generating of the EPROI image includes:
 digitally signal processing the electron paramagnetic resonance signals to generate image data; 
 storing the image data; and 
 displaying the image data. 
 
     
     
       14. A method for electron paramagnetic resonance oxygen imaging (EPROI) of a volume of animal tissue in vivo in an animal, the method comprising:
 placing a reporter molecule in the animal; 
 establishing a static (DC) magnetic field on the volume of animal tissue; 
 transmitting an RF three-pulse sequence from a set of surface transmit coils, wherein the transmitted RF three-pulse sequence generates an excitation magnetic field in the volume of animal tissue and elicits an inversion-recovery T 1e  spin-lattice relaxation response from the volume of tissue; 
 receiving a set of RF signals from a set of surface receive coils, wherein the set of surface receive coils generates a sensed electrical signal in response to a sensed magnetic field in the volume of animal tissue, and wherein the set of transmit coils and the set of receive coils are oriented relative to one another such that the sensed electrical signal has little or no component directly due to the excitation magnetic field, and wherein the set of surface receive coils is configured to detect electron paramagnetic resonance signals in the volume of animal tissue; 
 generating an EPROI image of oxygen in the animal from the electron paramagnetic resonance signals using the inversion-recovery T 1e  spin-lattice relaxation response; 
 wherein the establishing of the static (DC) magnetic field includes generating electron-spin-aligning constant and gradient magnetic fields with a set of static magnetic-field coils; and 
 wherein the transmitting of the RF three-pulse sequence further includes:
 generating a plurality of pulse sets, wherein the generating of each one of the plurality of pulse sets includes:
 generating a first RF excitation magnetic field pulse having a plurality of RF cycles in a first direction orthogonal to the static (DC) magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue, 
 delaying for a first delay time, 
 generating a second RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, 
 delaying for a second delay time, 
 generating a third RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, and 
 delaying for a third delay time; 
 
 
 wherein for each of the plurality of pulse sets,
 the first, second and third RF excitation magnetic field pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence having a π-pulse as the first pulse, a T delay as the first delay, a π/2-pulse as the second pulse, a τ delay as the second delay, a π-pulse as the third pulse, a τ delay as the third delay, wherein the first, second and third pulses are each about 35 ns in duration, 
 wherein the π/2 pulse rotates a magnetization π/2 radians and the π-pulses rotate a magnetization π radians, 
 wherein τ=630 ns, 
 wherein T has a value in a range of about 500 ns to about 16,000 ns, and 
 wherein the cycles of RF have a frequency of about 250 MHz. 
 
 
     
     
       15. A method for electron paramagnetic resonance oxygen imaging (EPROI) of a volume of animal tissue in vivo in an animal, the method comprising:
 placing a reporter molecule in the animal; 
 establishing a static (DC) magnetic field on the volume of animal tissue, wherein the establishing of the static (DC) magnetic field includes generating electron-spin-aligning constant and gradient magnetic fields with a set of static magnetic-field coils; 
 transmitting a plurality of pulse sets that elicit an inversion-recovery T 1e  spin-lattice relaxation response from the volume of tissue, wherein each one of the plurality of pulse sets includes:
 a first RF excitation magnetic field pulse having a plurality of RF cycles in a first direction orthogonal to the static (DC) magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue, 
 a first delay time, 
 a second RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, 
 a second delay time, 
 a third RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, and 
 a third delay time; 
 
 receiving a set of RF electron paramagnetic resonance signals in the volume of animal tissue to measure the inversion-recovery T 1e  spin-lattice relaxation response in the volume of tissue; and 
 generating an EPROI image of oxygen in the animal from the set of RF electron paramagnetic resonance signals using the inversion-recovery T 1e  spin-lattice relaxation response, wherein for each of the plurality of pulse sets: 
 the first RF excitation magnetic field pulse is a pi pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin by pi radians; 
 the second RF excitation magnetic field pulse is a pi/2 pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin ½ pi radians; and 
 the third RF excitation magnetic field pulse is a pi pulse having a magnitude and duration selected to rotate an electron paramagnetic resonance spin pi radians. 
 
     
     
       16. The method of  claim 15 , wherein for each of the plurality of pulse sets, the first, second and third RF excitation magnetic field pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence. 
     
     
       17. The method of  claim 15 , further comprising:
 digitally signal processing the set of RF electron paramagnetic resonance signals to generate image data; 
 storing the image data; and 
 displaying the image data. 
 
     
     
       18. A method for electron paramagnetic resonance oxygen imaging (EPROI) of a volume of animal tissue in vivo in an animal, the method comprising:
 placing a reporter molecule in the animal; 
 establishing a static (DC) magnetic field on the volume of animal tissue, wherein the establishing of the static (DC) magnetic field includes generating electron-spin-aligning constant and gradient magnetic fields with a set of static magnetic-field coils; 
 transmitting a plurality of pulse sets that elicit a T 1e  spin-lattice relaxation response from the volume of tissue, wherein each one of the plurality of pulse sets includes:
 a first RF excitation magnetic field pulse having a plurality of RF cycles in a first direction orthogonal to the static (DC) magnetic field in the volume of animal tissue from a surface of the animal next to the volume of animal tissue, 
 a first delay time, 
 a second RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, 
 a second delay time, 
 a third RF excitation magnetic field pulse having a plurality of RF cycles in the first direction orthogonal to the static (DC) magnetic field, and 
 a third delay time; 
 
 receiving a set of RF electron paramagnetic resonance signals in the volume of animal tissue to measure T 1e  spin-lattice relaxation in the volume of tissue; and 
 generating an EPROI image of oxygen in the animal from the set of RF electron paramagnetic resonance signals using the T 1e  spin-lattice relaxation response, 
 wherein for different ones of the plurality of pulse sets, the second RF excitation magnetic field pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees for different ones of the plurality of pulse sets) relative to the first pulse, and the third pulses have RF cycles that are shifted in phase by a selected different amount (by about either 0 degrees, 90 degrees, 180 degrees or 270 degrees) relative to the first pulse. 
 
     
     
       19. The method of  claim 18 , further comprising:
 digitally signal processing the set of RF electron paramagnetic resonance signals to generate image data; 
 storing the image data; and 
 displaying the image data. 
 
     
     
       20. The method of  claim 18 , wherein for each of the plurality of pulse sets, the first, second and third RF excitation magnetic field pulses form an inversion recovery with electron-spin echo detection (IRESE) sequence.